VG5Q Inhibition Suppresses Proliferation of Endothelial and Cancer Cell Lines

Background: Angiogenesis is a process involved in the formation of new vessels, and is essential for tumor growth and metastases. Angiogenic factors are critical for the initiation of angiogenesis and maintenance of the vascular network. VG5Q is a newly discovered protein that acts as a potent angiogenic factor in promoting angiogenesis and has also been implicated in the vascular pathophysiology of Klippel-Trenaunay syndrome. However, little is known about its role in cancer progression. Method: In this study, VG5Q expression was screened using RT-PCR and Western blotting in the following cancer cell lines: breast (MCF-7), renal (Caki, ACHN), mesothelioma (H2373, H2596), ovarian (OVCAR5), lung (H226, A549) and pancreatic (Panc-1, MiaPaCa). Human umbilical vein endothelial cells (HUVEC) and blood outgrowth endothelial cells (BOEC) were also screened. Results: All cancer cell lines expressed high levels of VG5Q that were comparable to the levels expressed in endothelial cells. The only exception was MiaPaCa cells. In order to understand the biology of VG5Q in cancer cells, we used siRNA knockdown of VG5Q expression in the mesothelioma cell lines H2373 and H2596. Gene-specific silencing of VG5Q resulted in markedly decreased proliferation, invasion, and soft-agar colony formation in these cells. Furthermore, VG5Q silencing increased apoptosis as seen by an increase in annexin levels. Conclusion: VG5Q silencing has profound effects on cancer cell biology, suggesting the hypothesis that the role of VG5Q may not be limited to angiogenic signaling in endothelial cells.